A Dose-Defining Study of CXL-1020 in Patients With Systolic Heart Failure

NCT01096043 | Completed Phase 2 DMC

• 1 other identifier: CXL-1020-02
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 15

Brief Summary

Study CXL-1020-02 employs is designed to further define suitable clinical dosages for CXL-1020 which will be utilized in a later Phase IIb study. The study is conducted in 3 different stages called 'strata" and evaluates the potential utility of this drug for the treatment of patents who are hospitalized with heart failure.

Conditions

Heart Failure

Keywords

Heart Failure; ADHF

Outcome Measures

Primary Outcomes (1)

• Safety and Hemodynamic Effects

  Define the safety and hemodynamic benefit of CXL-1020 based upon the change from baseline in hemodynamic measurements at the 6 hour time point in all strata

  At 6 Hours following start of dosing

Secondary Outcomes (5)

• Measurement of Plasma BNP Levels

  At 6 hours following the start of dosing

• Assessment of the dose/plasma concentration/effect relationship of CXL-1020

  At 6 hours following start of dosing

• Effects of CXL-1020 on Renal Function

  24 hours post dosing

• Signs and Symptoms of Heart failure

  At 6 hours following the start of dosing

• Evaluation of all Adverse Events

  Through 30 days following study drug dosing

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Each Strata of the study will have a placebo control. In strata A, the chance of getting active drug is 4 out of 5, in Strata B the chance of getting active drug is 3 ot of 4, and in Strata C, the chance of getting active Drug is 4 out of 5. In the event that a patient is allocated to receive placebo, the treatment may be stopped if the patient's condition fails to improve or worsens during the placebo infusion.

Drug: Placebo

Strata 1 CXL-1020

EXPERIMENTAL

Patients assigned to CXL-1020 in strata one will have their dose increased from the initial dose 2 times during the study period. The treatment may be stopped if the patient's condition fails to improve or worsens during the infusion.

Drug: Strata 1 CXL-1020

Strata 2 CXL-1020

EXPERIMENTAL

In strata 2, patients who are assigned to active treatment will receive one of up to 3 possible fixed dose levels of CXL-1020 for a period of 6 hours. The treatment may be stopped if the patient's condition fails to improve or worsens during the infusion.

Drug: Strata 2 CXL-1020

Strata 3 CXL-1020

EXPERIMENTAL

In strata 3, patients assigned to receive CXL-1020 will receive a fixed dose of CXL-1020 for 6 hours, and then the dose may be increased or decreased, based on the investigators assessment of the patient. The treatment may be stopped if the patient's condition fails to improve or worsens during the infusion.

Drug: Strata 3 CXL-1020

Interventions

Placebo DRUG

An infusion of an identically appearing solution of sugar water will be intravenously administered.

Also known as: BMS-986233

Placebo

Strata 1 CXL-1020 DRUG

Intravenous infusion of CXL-1020, up-titrated, so that 3 different dosages are administered over 6 hours

Also known as: BMS-986233

Strata 1 CXL-1020

Strata 2 CXL-1020 DRUG

One of 3 different dosages of CXL-1020 administered at a fixed dosage level for 6 hours.

Also known as: BMS-986233

Strata 2 CXL-1020

Strata 3 CXL-1020 DRUG

A fixed dose level of CXL-1020 will be administered for the initial 6 hours of treatment in Strata 3 and then dosage will be altered up or downward based on the investigators observation of the patient's condition.

Also known as: BMS-986233

Strata 3 CXL-1020

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In order to be eligible for randomization, a patient MUST:
• Be a male or post menopausal or surgically sterile female requiring inpatient evaluation or treatment and be between 18 and 85 years of age
• Not require immediate emergent treatment with conventional parenteral inotropes or vasodilators
• Be receiving standard background heart failure therapies as indicated, but not receive an oral dose of a hemodynamically active treatment or diuretic within 3 hours of baseline hemodynamic assessments
• Have chronic Systolic HF due to primary/idiopathic dilated cardiomyopathy, coronary artery disease or hypertension
• Have an elevated baseline BNP of at least 400pg/ml in all protocol strata
• Be capable of understanding the nature of the trial and be willing to participate as documented by written informed consent
• Be willing and able to comply with the inpatient and outpatient study protocol requirements for the duration of the study (treatment plus 30 follow up at days)
• If a post-menopausal or surgically sterile female, confirmation of sterility status (post-menopausal or surgically sterile for at least 6 months; post-menopausal subjects will require a urine pregnancy test for confirmation)
• If a fertile male, must be using 2 approved contraceptive methods (a condom and a spermicidal agent, even if partner(s) is using birth control) for 10 days following participation in the study and further agree to not donate sperm for 10 days after participation in the study
• Must have a negative urine test for drugs of abuse and a negative ethanol breath test or blood test at baseline before dosing
• May be receiving ICD, Bi V pacing or rate control pacing at the time of randomization so long as no alteration of settings are anticipated within the day of study drug administration

You may not qualify if:

• In order to be eligible for randomization, a patient MUST NOT:
• Have participated in any investigational drug study, SERCa gene therapy or cellular myocardial transplant study within 30 days preceding randomization or have previously received therapy with CXL-1020
• Have received a parenteral or oral dose of diuretics or other hemodynamically active therapy within 3 hours of the baseline hemodynamic assessment
• Have received intravenous inotropes, inodilators or vasodilators (amrinone, digoxin, dopamine, dobutamine, enoximone, levosimendan, milrinone, nesiritide, nitroglycerine or nitroprusside) for more than 4 hours and within 12 hours prior to randomization to treatment with study drug
• Have a heart rate \<50 or ≥ 90 BPM at baseline prior to randomization
• Have a blood pressure \>150 Systolic and/or \>95 diastolic mmHg at baseline prior to randomization
• Have a systolic blood pressure of less than 100 mmHg at baseline prior to randomization
• Be in atrial fibrillation/flutter at the time of randomization or have a history of recent intermittent A-fib/flutter within the previous week
• Have non-sustained VT (HR \> 120 bpm) of 10 beats or more during bedside monitoring prior to randomization or excessive VPB's or complex multifocal ventricular ectopy exceeding 10 beats per minute on a 2 minute rhythm strip taken within 10 minutes prior to randomization
• Be hospitalized with acute coronary syndrome or acute myocardial infarction during the previous 90 days prior to randomization
• Have a history of stroke (CVA) or transient ischemic attack (TIA) within six months prior to randomization
• Have a concurrent history of CCS Class III or IV angina
• Be a patient whose HF etiology is attributable to either restrictive/obstructive cardiomyopathy, idiopathic hypertrophic cardiomyopathy (as defined by any wall thickness \> 1.8 cm) or uncorrected severe valvular disease
• Be receiving concomitant oral or parenteral therapy with any antiarrhythmic drugs other than amiodarone or dronedarone. (only oral therapy is allowed for these agents)
• Have unsuitable echocardiographic windows for the Echo assessments (applies only to Strata B)

Sponsors & Collaborators

• Bristol-Myers Squibb: lead
• Cardioxyl Pharmaceuticals, Inc: collaborator

Study Sites (15)

University of Florida

Gainesville, Florida, 32610, United States

Location

University of Florida

Jacksonville, Florida, 32209, United States

Location

Florida Hospital Transplant Center

Orlando, Florida, 32804, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

DMC Cardiovascular Institute

Detroit, Michigan, 48201, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

University of Medicine & Dentistry of New Jersey - New Jersey Medical School

South Orange, New Jersey, 07103, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

University Hospitals Case Medical Center

Cleveland, Ohio, 44106, United States

Location

Davis Heart & Lung Research Institute

Columbus, Ohio, 43210, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Stern Cardiovascular Center PA

Germantown, Tennessee, 38138, United States

Location

Related Publications (1)

• Sabbah HN, Tocchetti CG, Wang M, Daya S, Gupta RC, Tunin RS, Mazhari R, Takimoto E, Paolocci N, Cowart D, Colucci WS, Kass DA. Nitroxyl (HNO): A novel approach for the acute treatment of heart failure. Circ Heart Fail. 2013 Nov;6(6):1250-8. doi: 10.1161/CIRCHEARTFAILURE.113.000632. Epub 2013 Oct 9.

  PMID: 24107588 DERIVED

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Wilson Colucci, M.D.

  Boston University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2010
• First Posted: March 30, 2010
• Study Start: April 1, 2010
• Primary Completion: February 1, 2012
• Study Completion: February 1, 2012
• Last Updated: November 15, 2016

Record last verified: 2012-04

Locations

US (15)